摘要
目的探讨21-羟化酶缺乏症(21-OHD)女婴临床特点、基因突变类型及表型基因型的关联,以期为21-OHD表型-基因型的关联提供新的证据,为21-OHD儿童的分子诊断及个体化管理提供依据。方法回顾分析2016年1月至2018年4月经郑州儿童医院内分泌遗传代谢科确诊的6例21-OHD女婴的临床和基因检测资料。采用Sanger测序和多重连接探针扩增技术,对CYP21A2基因外显子区域检测点突变和大片段缺失,分析临床表型与基因型的相关性。结果 6例女婴多以外生殖器异常及体重不增就诊,其中5例属于失盐型,1例属于单纯男性化型。5例失盐型基因检测结果分别为I2G/Ex. 1-7del(1例)、I2G/I2G (2例)、I2G,p. Q319X/p. R357W(1例)、p. Q319X/I2G(1例),均属于基因型Group A; 1例单纯男性化型基因检测结果为I2G/p. I173N,属于基因型Group B。本研究表型-基因型关联支持率为100%。结论女婴出现外生殖器畸形伴体重不增就诊时应考虑先天性肾上腺皮质增生症诊断,应及时完善相关实验室检查以明确诊断,并进一步行基因检测,以制定更加个体化的管理及随访方案。女婴21-OHD基因型-表型关联度较高。同时也提示推广21-OHD新生儿早期筛查工作的必要性。
Object To explore the clinical characteristics,gene mutation type,phenotype-genotype correlation of 21-hydroxylase deficiency( 21-OHD) in female infants to provide new evidence for phenotype-genotype correlation of 21-OHD and for molecular diagnosis and individual management of 21-OHD children. Methods The data of clinical and genetic testing of 6 female infants with 21-OHD diagnosed definitely by Zhengzhou Children’s Hospital from January 2016 to April2018 was retrospectively analyzed. Using Sanger sequencing and multiplex ligation-dependent probe amplification( MLPA),point mutation and large deletion in exon region of CYP21 A2 gene were detected to analyze the relationship between clinical phenotype and genotype. Results Six female infants presented mainly with enternal genital abnormalities and no weight gain,of which 5 cases belonged to phenotype of salt wasting,and 1 case belonged to phenotype of simple virilizing( SV). Genetic testing results for 5 cases of salt wasting phenotype were respectively I2 G/Ex. 1-7 del( 1 case),I2 G/I2 G( 2 cases),I2 G,p. Q319 X/p. R357 W( 1 case),p. Q319 X/I2 G( 1 case),which all belonged to group A mutation,and I2 G/p. I173 N for one simple SV type,which belonged to group B mutation. In the six cases,the support rate of phenotype-genotype correlation was 100%. Conclusions The diagnosis of congenital adrenal hyperplasia should be considered when the baby has an external genital malformation with weight loss. The relevant laboratory tests and further genetic testing should be completed in time to make a definite diagnosis,and further genetic testing must be carried out in order to formulate a more individualized management and follow-up plan. The genotype and phenotype has a good consistency in 21-OHD female infants. It also suggests the necessity of promoting early screening of 21-OHD newborns.
作者
王会贞
卫海燕
毋盛楠
沈凌花
杨海花
陈永兴
WANG Hui-zhen;WEI Hai-yan;WU Sheng-nan;SHEN Ling-hua;YANG Hai-hua;CHEN Yong-xing(Department of Endocrinology and Genetic Metabolism,Children's Hospital Affiliated to Zhengzhou University, Zhengzhou,Henan 450052,China)
出处
《中国临床研究》
CAS
2019年第1期81-84,共4页
Chinese Journal of Clinical Research
